Disproportionate dwarfism has been reported in many cattle breeds including Dexter, Holstein, Aberdeen Angus, Hereford and Shorthorn breeds. Dwarfism in American Angus has not been reported since the 1970's until recently when several calves from some sire×dam crosses resulted in phenotypically dwarf calves. Gross and histopathological examination of these calves indicated evidence for diminished endochondral ossification and exhibited other gross features consistent with dwarfism such as the protrusion of the alar wing of the basisphenoid bone into the cranial cavity, abnormalities of the ventral vertebral bodies, and curving of the transverse vertebral processes.
Many researchers have attempted to locate and identify the specific mutations associated with dwarfism, but this has met with only sporadic success. The desire for genetic tests to identify carriers of this condition has long been desirable, but has had limited success. Bovine chondrodysplastic dwarfism in Japanese brown cattle has been the subject of much research, See, for example, Takami, M.; Yoneda, K.; Kobayashi, Y.; Moritomo, Y.; Kata, S. R.; Womack, J. E.; Kunieda, T. “The bovine fibroblast growth factor receptor 3 (FGFR3) gene is not the locus responsible for bovine chondrodysplastic dwarfism in Japanese brown cattle” Animal Genetics: Volume 33(5) October 2002 p 351-355, Until it was ultimately mapped to the distal end of bovine chromosome 6 by linkage analysis. Disease-specific mutations in limbin were identified in affected dwarf calves. This mutation has not been shown to be associated with other types of breeds including Angus, Mishra, B. P.; Reecy, J. M “Mutations in the limbin gene previously associated with dwarfism in Japanese brown cattle are not responsible for dwarfism in the American Angus breed” Animal Genetics: Volume 34(4) August 2003 p 311-312
Presently, the only tool available for dwarfism diagnosis is patho-anatomical diagnosis based on the above described presence of phenotypic characteristics. Thus, there is great demand in the cattle industry for a genetic test that permits the identification of cattle in various breeds that are potential carriers of dwarfism (e.g. before detectable onset of clinical symptoms).
Prior to the present invention, the underlying molecular mechanism of dwarfism in cattle other than Japanese brown cattle has not been isolated or characterized.
It is an object of the present invention to provide a genetic test for dwarfism in Angus and other cattle breeds.
It is yet another object of the present invention to provide the molecular basis for characterizing and further understanding the dwarfism condition in cattle.
It is yet another object of the present invention to use the above information to identify other mutations in linkage disequilibrium with or that are causative of the condition in specific lines, populations or breeds.
Other objects will become apparent from the detailed description of the invention which follows.